10/30/2017 Familial Mediterranean Fever (Juvenile)

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Familial Mediterranean Fever (Juvenile)

Fast FactsFamilial Mediterranean Fever (FMF) is an inherited disorder,not an infectious one. It is a clinical diagnosis that can beconfirmed by a gene mutation in the majority of cases.FMF is diagnosed in children with episodic fevers, often withpain in the abdomen, joints, or chest. The fever of FMF is notcontagious.Life-long treatment for inflammation can prevent long-term injury to internal organs.

Familial Mediterranean Fever (FMF) is a genetic disorder that causes recurrent episodes of fever that are typicallyaccompanied by pain in the abdomen, chest, or joints. It most often occurs in individuals of Mediterranean and MiddleEastern descent, and the first episodes typically begin in childhood.

The disease generally affects people of Mediterranean and Middle Eastern descent, typically Sephardic Jews, Turks,Arabs, and Armenians. Since the discovery of the gene defect, it is being diagnosed more frequently, even amongpopulations where it was thought to be very rare, such as Italians, Greeks, Ashkenazi Jews, and even Asianpopulations. FMF episodes start before the age of 20 years in approximately 90% of the patients. In about 75% ofpatients, fever appears before the age of 10 years. FMF can appear or be active in adults, but often the disease ismilder and less obvious (and harder to diagnose) than in children.

The main symptoms of Familial Mediterranean Fever are recurrent episodes of fever, accompanied by abdominal,chest, or joint pain. Not all children will have all the symptoms, and symptoms may change over time. Episodesusually last one - three days and go away without treatment. Most children look and feel healthy betweenepisodes, but some children have such frequent episodes they do not fully recover or do not grow properly.Some of the episodes may be so painful that the patient or family seeks medical help in the emergencydepartment. Severe abdominal pain may look like appendicitis, and some patients may undergo surgery toremove the appendix. The chest pain may be so severe that it is difficult to breathe deeply.

What are the main symptoms of Familial Mediterranean Fever?

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Joint pain may accompany the episodes of fever. Usually, only one joint is affected at a time, most commonly anankle or a knee. The joint may be so swollen and painful that the child cannot walk. One-third of patients mayhave a red rash over the lower extremities, usually near the ankles and feet. In some children, the only finding ofthe disease may be episodes of joint pain and swelling, which can be misdiagnosed as acute rheumatic fever orjuvenile idiopathic arthritis. Usually the joint swelling resolves over 5 - 14 days, but sometimes may becomechronic (long-term).

Some children report muscle pain in the legs, especially after physical exertion. Rarely, children have recurrentpericarditis (inflammation of the outer layer of the heart), myositis (muscle inflammation), meningitis (inflammationof the membrane surrounding the brain and spinal cord), or orchitis (testicular inflammation). Children less thanfive years old may only have episodes of recurrent fever without other symptoms.

FMF has traditionally been considered a genetic disease caused by recessive genes. The responsible gene iscalled the MEFV gene. That means for FMF to occur, children must inherit two abnormal copies of the MEFVgene - one from the mother and one from the father. The parents are then called carriers. Often, someone in theextended family has the disease. If one child has the disease and the parents are carriers, there is a 25% chancethat another child will get FMF. If one child and one of the parents have FMF, there is a 50% chance of anotherchild getting FMF. However, how the disease is transmitted from one generation to the next has recently beenbrought into question since about 30% of FMF patients have just one abnormal gene or none at all.

The MEFV gene affects a protein called pyrin. Pyrin plays a role in the natural control of inflammation. When theMEFV gene does not work correctly, inflammation gets out of control, and patients experience episodes of feverand pain. Infection, trauma, strenuous exercise, menstrual periods, or psychological stress may trigger episodesof fever in FMF.

A test to look for gene mutations will be done in cases where FMF is suspected. If these tests are positive, thediagnosis of FMF is definite. It is possible to have FMF and have a defect in just one gene or none at all. In theUnited States, more than 30% of the patients with FMF do not have mutations in both genes. Therefore, thediagnosis of FMF is still based on symptoms and physical examination by the physician, and can be difficult.

FMF is suspected in children with periodic (episodic) fever and an ethnic background common for FMF. A familymember may also have FMF or unexplained kidney failure. Often children, especially those younger than fiveyears of age, initially have periodic fevers without the other symptoms, so it takes careful observation to make adiagnosis. Families can help by keeping a diary documenting when the fevers happen. Examining the childduring a fever and obtaining laboratory tests that show signs of inflammation can be helpful.

In some cases a medication called colchicine, will be given for three - six months as a test. If episodes of painand fever are less frequent on colchicine treatment, this may make the diagnosis of FMF.

What causes Familial Mediterranean Fever?

How is Familial Mediterranean Fever diagnosed?

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FMF cannot be cured, but it can be controlled with life-long use of colchicine, a medication that is taken bymouth one - two times a day. Colchicine prevents episodes from starting, but does not treat an episode that hasalready started. Therefore, the dose of colchicine should not be increased during an active episode. If the patientstops taking the medicine, episodes may return even after missing only one dose. If colchicine is taken regularly,the vast majority of children with FMF can live a normal life with a normal life expectancy. Do not change themedication dose without first discussing it with your doctor.

The most common side effects of colchicine are abdominal pain and diarrhea. If this occurs, the dose can bereduced until it is tolerated and then slowly increased back to the appropriate dose. Reducing the intake of milkor other dairy products, or consuming lactose-free milk may help. Other side effects are nausea, vomiting, andabdominal cramps. In rare cases, colchicine may cause muscle weakness, especially when taking antibioticsfrom the erythromycin (macrolide) family or statins (cholesterol medications). Therefore, these medications needto be given with caution with colchicine. The blood counts (white and red blood cells and platelets) maydecrease occasionally and there may be mild elevations in liver enzymes, but these usually recover with dosereduction. Children taking colchicine grow normally.

Female patients do not have to stop taking colchicine during pregnancy or breast-feeding, but amniocentesis(obtaining fluid from the fluid surrounding the fetus) is recommended by most authorities. Children treated withcolchicine should have blood and urine tests at least twice yearly.

About ten percent of patients do not respond adequately or cannot tolerate colchicine. Recent research hasfound that medications that block interleukin-1, an important protein involved in the inflammatory process, maybe effective for the majority of these patients. These medications include rilonacept (Arcalyst), anakinra (Kineret),and canakinumab (Ilaris).

The most severe complication of untreated FMF is the development of amyloidosis. Amyloid is a protein thatdeposits in the organs of children who have chronic inflammatory diseases that are not well controlled. The mostcommon organ involved is the kidney, but amyloid can deposit in the intestines, skin, and heart. Eventually,amyloid causes a loss of function, especially in the kidneys. If this occurs, dialysis or a kidney transplant mightbe necessary. Children who are properly treated with colchicine are safe from the risk of developing this life-threatening complication, but stopping treatment even for a short while can allow amyloidosis to occur. Patientswith amyloidosis in the kidney will have high levels of protein in urine tests. Patients with FMF should have urinetests at least twice a year.

Some children initially need psychological support to cope with a disease that means taking medications for theirentire lives. Frequent episodes can affect the both the child and family life, including school attendance, soinvolvement of teachers, social workers, tutors, and other community members may be helpful. Most children,

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